The objectives are: (1) To elucidate hypothalamic regulation of anterior pituitary (AP) function, with particular emphasis on the role of catecholamines, serotonin, acetylcholine, GABA and brain opiate peptides. These neurotransmitters will be measured in the hypothalamus together with serum AP hormone levels (prolactin, GH, LH, FSH, TSH) during different endocrine states (castration, steroid hormone administration, stress, lactation, pregnancy, aging, drug treatment, dietary deficiencies, etc.). (2) Enkephalins, endorphins and their antagonists (naloxone, naltroxone, etc.) will be given to rats to determine whether these can influence basal serum AP hormone levels, and to see whether they can modify the effects of stress, suckling, castration, estrogen, cervical stimulation, drugs, etc. on AP hormone levels. Studies will also be done to determine the effects of brain opiate peptides on hypothalamic content and turnover of biogenic amines. (3) Further studies will be done on the relation of the neuroendocrine system to reproductive senescence, to other aging processes, and to development and growth of mammary and pituitary tumors. Neurotransmitters will be measured in the hypothalamus; and AP, gonadal and adrenal cortical steroids will be assayed by RIAs the serum. Old male and female animals will be challenged with CNS active drugs, and with hormones and other stimuli in attempts to inhibit or prevent aging changes. (4) Studies will be done to determine whether the "short-loop feedback" has a physiological role in control of AP hormone secretion, by observing the effects of injecting prolactin and GH on hypothalamic neurotransmitters and by seeing whether physiological increases in circulating levels of these 2 hormones can depress secretion of these hormones by the AP. (5) Attempts will be made to clarify the question of whether dopamines and PIF (prolactin release inhibiting factor) are one and the same.